User login
Intranasal midazolam as first line for status epilepticus
BANGKOK – Lara Kay, MD, said at the International Epilepsy Congress.
Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.
“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.
While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.
Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.
Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.
The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.
Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.
“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.
Dr. Kay reported having no financial conflicts of interest regarding her study.
SOURCE: Kay L et al. IEC 2019, Abstract P029.
BANGKOK – Lara Kay, MD, said at the International Epilepsy Congress.
Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.
“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.
While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.
Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.
Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.
The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.
Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.
“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.
Dr. Kay reported having no financial conflicts of interest regarding her study.
SOURCE: Kay L et al. IEC 2019, Abstract P029.
BANGKOK – Lara Kay, MD, said at the International Epilepsy Congress.
Why? Because status epilepticus is a major medical emergency. It’s associated with substantial morbidity and mortality. And of the various factors that influence outcome in status epilepticus – including age, underlying etiology, and level of consciousness – only one is potentially within physician control: time to treatment, she noted at the congress sponsored by the International League Against Epilepsy.
“Time is brain,” observed Dr. Kay, a neurologist at the epilepsy center at University Hospital Frankfurt.
While intravenous benzodiazepines – for example, lorazepam at 2-4 mg – are widely accepted as the time-honored first-line treatment for status epilepticus, trying to place a line in a patient experiencing this emergency can be a tricky, time-consuming business. Multiple studies have demonstrated that various nonintravenous formulations of benzodiazepines, such as rectal diazepam or buccal or intramuscular midazolam, can be administered much faster and are as effective as intravenous benzodiazepines. But buccal midazolam is quite expensive in Germany, and the ready-to-use intramuscular midazolam applicator that’s available in the United States isn’t marketed in Germany. So several years ago Dr. Kay and her fellow neurologists started having their university hospital pharmacy manufacture intranasal midazolam.
Dr. Kay presented an observational study of 42 consecutive patients with status epilepticus who received intranasal midazolam as first-line treatment. The patients had a mean age of nearly 53 years and 23 were women. The starting dose was 2.5 mg per nostril, moving up to 5 mg per nostril after waiting 5 minutes in initial nonresponders.
Status epilepticus ceased both clinically and by EEG in 24 of the 42 patients, or 57%, in an average of 5 minutes after administration of the intranasal medication at a mean dose of 5.6 mg. Nonresponders received a mean dose of 7.5 mg. There were no significant differences between responders and nonresponders in terms of the proportion presenting with preexisting epilepsy or the epilepsy etiology. However, responders presented at a mean of 54 minutes in status epilepticus, while nonresponders had been in status for 17 minutes.
The 57% response rate with intranasal midazolam is comparable with other investigators’ reported success rates using other benzodiazepines and routes of administration, she noted.
Session cochair Gregory Krauss, MD, commented that he thought the Frankfurt neurologists may have been too cautious in their dosing of intranasal midazolam for status epilepticus.
“Often in the U.S. 5 mg is initially used in each nostril,” according to Dr. Krauss, professor of neurology at Johns Hopkins University, Baltimore.
Dr. Kay reported having no financial conflicts of interest regarding her study.
SOURCE: Kay L et al. IEC 2019, Abstract P029.
REPORTING FROM IEC 2019
Opioid Epidemic
Recent progress in vitiligo treatment might be heading to vitiligo cure
NEW YORK – but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.
Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.
In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.
As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.
“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.
However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.
These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.
In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.
This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.
Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.
“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.
In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.
Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.
It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.
“Based on these data, we are expecting clinical trials soon,” he said.
Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.
NEW YORK – but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.
Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.
In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.
As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.
“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.
However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.
These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.
In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.
This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.
Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.
“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.
In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.
Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.
It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.
“Based on these data, we are expecting clinical trials soon,” he said.
Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.
NEW YORK – but also might be leading to a strategy that will prevent the inevitable relapse that occurs after treatment is stopped, according to an update at the American Academy of Dermatology summer meeting.
Recently, trial results with a Janus kinase (JAK) pathway inhibitor have shown promise for treatment of vitiligo, but the ultimate fix for this recurring autoimmune disease might be elimination of resident-memory T cells, according to John Harris, MD, PhD, of the department of dermatology at the University of Massachusetts, Worcester.
In a murine vitiligo model, targeting interleukin-15, a cytokine thought to be essential for maintaining memory T cells, produced rapid and durable repigmentation without apparent adverse effects in a series of studies sufficiently promising that clinical trials are now being actively planned, Dr. Harris said. The ongoing work to eliminate resident-memory T cells to prevent relapse of vitiligo comes at the end of other recent advances that have provided major insights into the pathophysiology of vitiligo.
As outlined by Dr. Harris, vitiligo involves an autoimmune sequence that includes up-regulation of interferon-gamma, activation of the JAK signaling pathway, and mobilization of the cytokine CXCl10, all of which are part of the sequence of events culminating in activation of T cells that attack the melanocyte. The process can be stopped when any of these events are targeted, according to the experimental studies. These findings have already been translated into new drug development.
“There are now three ongoing clinical trials with JAK inhibitors. This is a tremendous advance in a disease for which there have been no clinical trials for decades,” Dr. Harris said. He cited highly positive data with the JAK inhibitor ruxolitinib, which were reported just weeks earlier at the World Congress of Dermatology, to confirm that this principle of intervention is viable.
However, relapse after discontinuation of ruxolitinib, like other treatments for vitiligo, is high. The observation that relapses typically occur in the exact spot where skin lesions occurred previously created the framework of a new potential wave of advances, according to Dr. Harris, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester.
These advances involve progress in understanding the role of resident-memory T cells in driving autoimmune disease relapse.
In principle, memory-resident T cells are left behind in order to stimulate a rapid immune response in the event of a recurrence of a virus or another pathogen. According to work performed in animal models of vitiligo, they also appear to play a critical role in reactivation of this autoimmune disease, Dr. Harris said.
This role was not surprising, but the potential breakthrough in vitiligo surrounds evidence that the cytokine IL-15 is essential to the creation and maintenance of these memory cells. Evidence suggests vitiligo in animal models does not recur in the absence of IL-15, making it a potential target for treatment.
Initially, there was concern that inhibition of IL-15 would have off-target effects, but this concern has diminished with antibodies designed to inhibit IL-15 signaling in the animal model.
“It turns out that autoreactive cells are much more dependent on the cytokine than other T cells,” he said.
In the animal model, repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, these mice then appear to be protected from vitiligo recurrence for extended periods, Dr. Harris noted.
Studies conducted with human tissue have provided strong evidence that the same mechanisms are in play. There are now several approaches to blocking IL-15 signaling, including a monoclonal antibody targeted at the IL-15 receptor, in development. This latter approach is now the focus of a company formed by Dr. Harris.
It is not yet clear if one approach to the inhibition of IL-15 will be superior to another, but Dr. Harris is highly optimistic that this will be a viable approach to control of vitiligo. Noting that good results have been achieved in experimental models by skin injections, thereby avoiding systemic exposure, he is also optimistic that this approach will be well tolerated.
“Based on these data, we are expecting clinical trials soon,” he said.
Dr. Harris reported serving as a consultant and/or investigator for multiple pharmaceutical companies including Aclaris Therapeutics, Celgene, EMD Serono, Genzyme, Incyte, and Janssen Biotech.
EXPERT ANALYSIS FROM SUMMER AAD 2019
A practical tool predicts childhood epilepsy diagnosis
BANGKOK – A prediction tool that determines the risk of a pediatric epilepsy diagnosis eventually being made in a child who has had one or more paroxysmal events of possible epileptic origin is now available, and the clarity it provides makes life considerably easier for physicians and worried parents, Kees P. Braun, MD, PhD, said at the International Epilepsy Congress.
This prediction tool is highly practical. It relies upon certain clinical characteristics and a first interictal EEG, all information readily available at the time of the family’s first consultation with a neurologist or pediatrician with access to EEG, noted Dr. Braun, professor of neurology at Utrecht (the Netherlands) University.
The tool is freely available online (http://epilepsypredictiontools.info/first-consultation). The details of how Dr. Braun and coinvestigators developed the prediction tool have been published (Pediatrics. 2018 Dec;142[6]:e20180931. doi: 10.1542/peds.2018-0931), he said at the congress sponsored by the International League Against Epilepsy.
Early and accurate diagnosis or exclusion of epilepsy following a suspicious paroxysmal event deserves to be a high priority. Diagnostic delay is common, with resultant unrecognized recurrent epileptic seizures that can cause cognitive and behavioral impairments. And overdiagnosis of pediatric epilepsy unnecessarily exposes a child to the risks of antiepileptic drug therapy, not to mention the potential social stigma.
The predictive tool was developed through retrospective, multidimensional analysis of detailed data on 451 children who visited the outpatient pediatric neurology clinic at University Medical Center Utrecht for a diagnostic work-up after one or more paroxysmal events that might have been seizures, all of whom were subsequently followed for a year or longer. The resultant predictive model was then independently validated in a separate cohort of 187 children seen for the same reason at another Dutch university.
The model had an area under the receiver operating characteristic curve of 0.86, which statisticians consider to be excellent discriminatory power. The tool’s sensitivity and specificity varied according to the diagnostic probability threshold selected by the parents and physicians. For example, the predictive tool had a sensitivity of 18%, specificity of 99%, positive predictive value of 94%, and negative predictive value of 80% for identification of individuals with a greater than 80% probability of being diagnosed with epilepsy. For identification of all patients with a greater than 20% likelihood of receiving the diagnosis, the sensitivity was 73%, specificity 82%, positive predictive value 76%, and negative predictive value 79%.
The clinical characteristics incorporated in the predictive model include age at first seizure, gender, details of the paroxysmal event, and specifics of the child’s medical history. The relevant features of the standard interictal EEG recorded at the time of consultation include the presence or absence of focal epileptiform abnormalities if focal spikes or spike-wave complexes were detected, generalized epileptiform abnormalities in the presence of generalized spikes or spike-wave complexes, and nonspecific nonepileptiform abnormalities.
Future predictive refinements are under study
Dr. Braun and coworkers have reported that examining EEG functional network characteristics – that is, the functional networks of correlated brain activity in an individual patient’s brain – improves the EEG’s predictive value for epilepsy (PLoS One. 2013;8[4]:e59764. doi: 10.1371/journal.pone.0059764), a conclusion further reinforced in their systematic review and meta-analysis incorporating 11 additional studies (PLoS One. 2014 Dec 10;9[12]:e114606. doi: 10.1371/journal.pone.0114606).
In addition, the Dutch investigators have shown that ripples superimposed on rolandic spikes seen in scalp EEG recordings have prognostic significance. An absence of ripples superimposed on rolandic spikes identified children without epilepsy. In contrast, more than five ripples predicted atypical and symptomatic rolandic epilepsy with a substantial seizure risk warranting consideration of antiepileptic drug therapy (Epilepsia. 2016 Jul;57[7]:1179-89).
A Boston group using a fully automated spike ripple detector subsequently confirmed that ripples occurring in conjunction with epileptiform discharges on scalp EEG constitute a noninvasive biomarker for seizure risk that outperforms analysis of spikes alone and could potentially be useful in guiding medication tapering decisions in children (Brain. 2019 May 1;142[5]:1296-1309).
Dr. Braun reported having no financial conflicts regarding his presentation.
BANGKOK – A prediction tool that determines the risk of a pediatric epilepsy diagnosis eventually being made in a child who has had one or more paroxysmal events of possible epileptic origin is now available, and the clarity it provides makes life considerably easier for physicians and worried parents, Kees P. Braun, MD, PhD, said at the International Epilepsy Congress.
This prediction tool is highly practical. It relies upon certain clinical characteristics and a first interictal EEG, all information readily available at the time of the family’s first consultation with a neurologist or pediatrician with access to EEG, noted Dr. Braun, professor of neurology at Utrecht (the Netherlands) University.
The tool is freely available online (http://epilepsypredictiontools.info/first-consultation). The details of how Dr. Braun and coinvestigators developed the prediction tool have been published (Pediatrics. 2018 Dec;142[6]:e20180931. doi: 10.1542/peds.2018-0931), he said at the congress sponsored by the International League Against Epilepsy.
Early and accurate diagnosis or exclusion of epilepsy following a suspicious paroxysmal event deserves to be a high priority. Diagnostic delay is common, with resultant unrecognized recurrent epileptic seizures that can cause cognitive and behavioral impairments. And overdiagnosis of pediatric epilepsy unnecessarily exposes a child to the risks of antiepileptic drug therapy, not to mention the potential social stigma.
The predictive tool was developed through retrospective, multidimensional analysis of detailed data on 451 children who visited the outpatient pediatric neurology clinic at University Medical Center Utrecht for a diagnostic work-up after one or more paroxysmal events that might have been seizures, all of whom were subsequently followed for a year or longer. The resultant predictive model was then independently validated in a separate cohort of 187 children seen for the same reason at another Dutch university.
The model had an area under the receiver operating characteristic curve of 0.86, which statisticians consider to be excellent discriminatory power. The tool’s sensitivity and specificity varied according to the diagnostic probability threshold selected by the parents and physicians. For example, the predictive tool had a sensitivity of 18%, specificity of 99%, positive predictive value of 94%, and negative predictive value of 80% for identification of individuals with a greater than 80% probability of being diagnosed with epilepsy. For identification of all patients with a greater than 20% likelihood of receiving the diagnosis, the sensitivity was 73%, specificity 82%, positive predictive value 76%, and negative predictive value 79%.
The clinical characteristics incorporated in the predictive model include age at first seizure, gender, details of the paroxysmal event, and specifics of the child’s medical history. The relevant features of the standard interictal EEG recorded at the time of consultation include the presence or absence of focal epileptiform abnormalities if focal spikes or spike-wave complexes were detected, generalized epileptiform abnormalities in the presence of generalized spikes or spike-wave complexes, and nonspecific nonepileptiform abnormalities.
Future predictive refinements are under study
Dr. Braun and coworkers have reported that examining EEG functional network characteristics – that is, the functional networks of correlated brain activity in an individual patient’s brain – improves the EEG’s predictive value for epilepsy (PLoS One. 2013;8[4]:e59764. doi: 10.1371/journal.pone.0059764), a conclusion further reinforced in their systematic review and meta-analysis incorporating 11 additional studies (PLoS One. 2014 Dec 10;9[12]:e114606. doi: 10.1371/journal.pone.0114606).
In addition, the Dutch investigators have shown that ripples superimposed on rolandic spikes seen in scalp EEG recordings have prognostic significance. An absence of ripples superimposed on rolandic spikes identified children without epilepsy. In contrast, more than five ripples predicted atypical and symptomatic rolandic epilepsy with a substantial seizure risk warranting consideration of antiepileptic drug therapy (Epilepsia. 2016 Jul;57[7]:1179-89).
A Boston group using a fully automated spike ripple detector subsequently confirmed that ripples occurring in conjunction with epileptiform discharges on scalp EEG constitute a noninvasive biomarker for seizure risk that outperforms analysis of spikes alone and could potentially be useful in guiding medication tapering decisions in children (Brain. 2019 May 1;142[5]:1296-1309).
Dr. Braun reported having no financial conflicts regarding his presentation.
BANGKOK – A prediction tool that determines the risk of a pediatric epilepsy diagnosis eventually being made in a child who has had one or more paroxysmal events of possible epileptic origin is now available, and the clarity it provides makes life considerably easier for physicians and worried parents, Kees P. Braun, MD, PhD, said at the International Epilepsy Congress.
This prediction tool is highly practical. It relies upon certain clinical characteristics and a first interictal EEG, all information readily available at the time of the family’s first consultation with a neurologist or pediatrician with access to EEG, noted Dr. Braun, professor of neurology at Utrecht (the Netherlands) University.
The tool is freely available online (http://epilepsypredictiontools.info/first-consultation). The details of how Dr. Braun and coinvestigators developed the prediction tool have been published (Pediatrics. 2018 Dec;142[6]:e20180931. doi: 10.1542/peds.2018-0931), he said at the congress sponsored by the International League Against Epilepsy.
Early and accurate diagnosis or exclusion of epilepsy following a suspicious paroxysmal event deserves to be a high priority. Diagnostic delay is common, with resultant unrecognized recurrent epileptic seizures that can cause cognitive and behavioral impairments. And overdiagnosis of pediatric epilepsy unnecessarily exposes a child to the risks of antiepileptic drug therapy, not to mention the potential social stigma.
The predictive tool was developed through retrospective, multidimensional analysis of detailed data on 451 children who visited the outpatient pediatric neurology clinic at University Medical Center Utrecht for a diagnostic work-up after one or more paroxysmal events that might have been seizures, all of whom were subsequently followed for a year or longer. The resultant predictive model was then independently validated in a separate cohort of 187 children seen for the same reason at another Dutch university.
The model had an area under the receiver operating characteristic curve of 0.86, which statisticians consider to be excellent discriminatory power. The tool’s sensitivity and specificity varied according to the diagnostic probability threshold selected by the parents and physicians. For example, the predictive tool had a sensitivity of 18%, specificity of 99%, positive predictive value of 94%, and negative predictive value of 80% for identification of individuals with a greater than 80% probability of being diagnosed with epilepsy. For identification of all patients with a greater than 20% likelihood of receiving the diagnosis, the sensitivity was 73%, specificity 82%, positive predictive value 76%, and negative predictive value 79%.
The clinical characteristics incorporated in the predictive model include age at first seizure, gender, details of the paroxysmal event, and specifics of the child’s medical history. The relevant features of the standard interictal EEG recorded at the time of consultation include the presence or absence of focal epileptiform abnormalities if focal spikes or spike-wave complexes were detected, generalized epileptiform abnormalities in the presence of generalized spikes or spike-wave complexes, and nonspecific nonepileptiform abnormalities.
Future predictive refinements are under study
Dr. Braun and coworkers have reported that examining EEG functional network characteristics – that is, the functional networks of correlated brain activity in an individual patient’s brain – improves the EEG’s predictive value for epilepsy (PLoS One. 2013;8[4]:e59764. doi: 10.1371/journal.pone.0059764), a conclusion further reinforced in their systematic review and meta-analysis incorporating 11 additional studies (PLoS One. 2014 Dec 10;9[12]:e114606. doi: 10.1371/journal.pone.0114606).
In addition, the Dutch investigators have shown that ripples superimposed on rolandic spikes seen in scalp EEG recordings have prognostic significance. An absence of ripples superimposed on rolandic spikes identified children without epilepsy. In contrast, more than five ripples predicted atypical and symptomatic rolandic epilepsy with a substantial seizure risk warranting consideration of antiepileptic drug therapy (Epilepsia. 2016 Jul;57[7]:1179-89).
A Boston group using a fully automated spike ripple detector subsequently confirmed that ripples occurring in conjunction with epileptiform discharges on scalp EEG constitute a noninvasive biomarker for seizure risk that outperforms analysis of spikes alone and could potentially be useful in guiding medication tapering decisions in children (Brain. 2019 May 1;142[5]:1296-1309).
Dr. Braun reported having no financial conflicts regarding his presentation.
REPORTING FROM IEC 2019
Smoldering Lesions: Red Flags for Severe MS
“Smoldering” lesions—signaling chronic inflammation—may be a hallmark of more aggressive forms of multiple sclerosis (MS), according to researchers from the National Institute of Neurological Disorders and Stroke (NINDS). New technology that allows long-term in vivo monitoring could make it possible for the first time to predict who is at risk for progressive MS and potential treatments.
MS lesions appear as spots on brain scans. Some lesions heal. Others remain and may have characteristic dark rims, which is inflammatory demyelination at the edges. The dark-rimmed lesions appear to expand, or “smolder” for years. But until recently, researchers did not fully understand what role those chronic active lesions played in MS because it was difficult to find the ones that remain inflamed.
The researchers conducted 3 studies at the NIH Clinical Center. In the first, using a high-powered, 7-tesla MRI scanner and a 3D printer, they scanned the brains of 192 MS patients. Of those, 40% had no rimmed lesions; 32% had 1 to 3 rims; and 20% had ≥ 4 rims. Regardless of the treatment they were receiving, 56% of the patients had at < 1 rimmed lesion.
The researchers compared the brain scans to the patients’ baseline neurologic examinations. Patients with ≥ 4 rimmed lesions were nearly twice as likely to be diagnosed with progressive MS than were those without rimmed lesions. Moreover, the patients with rimmed lesions developed motor and cognitive disabilities at a younger age than did patients without rimmed lesions. Patients with ≥ 4 rimmed lesions also had less white matter and smaller basal ganglia.
When they analyzed a subset of patients whose brains had been scanned once a year for ≥ 10 years, the researchers found that although the rimless lesions generally shrank, the rimmed lesions grew or stayed the same size and were “particularly damaged.”
The team also used a 3D printer to compare the spots they had seen on scans with lesions in brain tissue samples from a patient who died during the trial. All 10 expanding rimmed spots on the scans had the “telltale features” of chronic active lesions when examined under a microscope.
“Figuring out how to spot chronic active lesions was a big step,” said research team member Martina Absinta, MD, PhD. “We could not have done it without the high-powered MRI scanner.” Most MRI scanners used clinically have field strengths of 1.5 or 3 Tesla. The research team had previously published instructions for programming lower powered MRI scanners to detect rimmed chronic active lesions.
Chronic active lesions are common and exert ongoing tissue damage, said Daniel S. Reich, MD, PHD, senior investigator at NINDS, and senior author of the paper. The fact that these lesions are present in patients who are receiving anti-inflammatory drugs, he added, suggests that the field of MS research may want to focus on new treatments that target the brain’s unique immune system—especially a type of brain cell called microglia, which are instrumental in the immune response.
Their findings, the researchers say, should prompt MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS. Dr. Reich said, “Our results point the way toward using specialized brain scans to predict who is at risk of developing progressive MS.”
“Smoldering” lesions—signaling chronic inflammation—may be a hallmark of more aggressive forms of multiple sclerosis (MS), according to researchers from the National Institute of Neurological Disorders and Stroke (NINDS). New technology that allows long-term in vivo monitoring could make it possible for the first time to predict who is at risk for progressive MS and potential treatments.
MS lesions appear as spots on brain scans. Some lesions heal. Others remain and may have characteristic dark rims, which is inflammatory demyelination at the edges. The dark-rimmed lesions appear to expand, or “smolder” for years. But until recently, researchers did not fully understand what role those chronic active lesions played in MS because it was difficult to find the ones that remain inflamed.
The researchers conducted 3 studies at the NIH Clinical Center. In the first, using a high-powered, 7-tesla MRI scanner and a 3D printer, they scanned the brains of 192 MS patients. Of those, 40% had no rimmed lesions; 32% had 1 to 3 rims; and 20% had ≥ 4 rims. Regardless of the treatment they were receiving, 56% of the patients had at < 1 rimmed lesion.
The researchers compared the brain scans to the patients’ baseline neurologic examinations. Patients with ≥ 4 rimmed lesions were nearly twice as likely to be diagnosed with progressive MS than were those without rimmed lesions. Moreover, the patients with rimmed lesions developed motor and cognitive disabilities at a younger age than did patients without rimmed lesions. Patients with ≥ 4 rimmed lesions also had less white matter and smaller basal ganglia.
When they analyzed a subset of patients whose brains had been scanned once a year for ≥ 10 years, the researchers found that although the rimless lesions generally shrank, the rimmed lesions grew or stayed the same size and were “particularly damaged.”
The team also used a 3D printer to compare the spots they had seen on scans with lesions in brain tissue samples from a patient who died during the trial. All 10 expanding rimmed spots on the scans had the “telltale features” of chronic active lesions when examined under a microscope.
“Figuring out how to spot chronic active lesions was a big step,” said research team member Martina Absinta, MD, PhD. “We could not have done it without the high-powered MRI scanner.” Most MRI scanners used clinically have field strengths of 1.5 or 3 Tesla. The research team had previously published instructions for programming lower powered MRI scanners to detect rimmed chronic active lesions.
Chronic active lesions are common and exert ongoing tissue damage, said Daniel S. Reich, MD, PHD, senior investigator at NINDS, and senior author of the paper. The fact that these lesions are present in patients who are receiving anti-inflammatory drugs, he added, suggests that the field of MS research may want to focus on new treatments that target the brain’s unique immune system—especially a type of brain cell called microglia, which are instrumental in the immune response.
Their findings, the researchers say, should prompt MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS. Dr. Reich said, “Our results point the way toward using specialized brain scans to predict who is at risk of developing progressive MS.”
“Smoldering” lesions—signaling chronic inflammation—may be a hallmark of more aggressive forms of multiple sclerosis (MS), according to researchers from the National Institute of Neurological Disorders and Stroke (NINDS). New technology that allows long-term in vivo monitoring could make it possible for the first time to predict who is at risk for progressive MS and potential treatments.
MS lesions appear as spots on brain scans. Some lesions heal. Others remain and may have characteristic dark rims, which is inflammatory demyelination at the edges. The dark-rimmed lesions appear to expand, or “smolder” for years. But until recently, researchers did not fully understand what role those chronic active lesions played in MS because it was difficult to find the ones that remain inflamed.
The researchers conducted 3 studies at the NIH Clinical Center. In the first, using a high-powered, 7-tesla MRI scanner and a 3D printer, they scanned the brains of 192 MS patients. Of those, 40% had no rimmed lesions; 32% had 1 to 3 rims; and 20% had ≥ 4 rims. Regardless of the treatment they were receiving, 56% of the patients had at < 1 rimmed lesion.
The researchers compared the brain scans to the patients’ baseline neurologic examinations. Patients with ≥ 4 rimmed lesions were nearly twice as likely to be diagnosed with progressive MS than were those without rimmed lesions. Moreover, the patients with rimmed lesions developed motor and cognitive disabilities at a younger age than did patients without rimmed lesions. Patients with ≥ 4 rimmed lesions also had less white matter and smaller basal ganglia.
When they analyzed a subset of patients whose brains had been scanned once a year for ≥ 10 years, the researchers found that although the rimless lesions generally shrank, the rimmed lesions grew or stayed the same size and were “particularly damaged.”
The team also used a 3D printer to compare the spots they had seen on scans with lesions in brain tissue samples from a patient who died during the trial. All 10 expanding rimmed spots on the scans had the “telltale features” of chronic active lesions when examined under a microscope.
“Figuring out how to spot chronic active lesions was a big step,” said research team member Martina Absinta, MD, PhD. “We could not have done it without the high-powered MRI scanner.” Most MRI scanners used clinically have field strengths of 1.5 or 3 Tesla. The research team had previously published instructions for programming lower powered MRI scanners to detect rimmed chronic active lesions.
Chronic active lesions are common and exert ongoing tissue damage, said Daniel S. Reich, MD, PHD, senior investigator at NINDS, and senior author of the paper. The fact that these lesions are present in patients who are receiving anti-inflammatory drugs, he added, suggests that the field of MS research may want to focus on new treatments that target the brain’s unique immune system—especially a type of brain cell called microglia, which are instrumental in the immune response.
Their findings, the researchers say, should prompt MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS. Dr. Reich said, “Our results point the way toward using specialized brain scans to predict who is at risk of developing progressive MS.”
Dermatologists lack training about skin of color
a small study in JAMA Dermatology suggests.
Lead author Kristina Gorbatenko-Roth, PhD, of the department of psychology at University of Wisconsin-Stout, Menomonie, Wis., and colleagues analyzed the perceptions of 19 black, adult patients who had received treatment in a skin of color clinic (SOCC). Patients were asked about their perspectives and experiences inside and outside of the clinic as it pertained to dermatologists’ interaction style, cultural awareness, and overall treatment. Two focus groups consisted of patients seen by a race-concordant dermatologist, and two focus groups consisted of patients seen by a race-discordant dermatologist. The patients also responded to a survey.
Of 19 adult black patients who participated in the study, 18 respondents were women, and the mean age was 50 years. Compared with non-SOCC dermatology treatment experiences, patients experienced higher levels of overall satisfaction with SOCC dermatologists, reporting that SOCC dermatologists were better trained to care for black patients, showed greater respect and dignity, and were more trustworthy, according to the study published Aug 21.
Care satisfaction appeared most related to doctors’ interpersonal style and specialized knowledge of black skin and hair, according to the study. Investigators gleaned nine major themes during the analysis, five of which included dermatologist behaviors: interaction style, knowledge, partnering with patients in focusing on outcomes, economic sensitivity, and shared life experiences. Four themes were specific to patients: comfort, confidence, education, and concordance preference. Across all participants, a dermatologist’s interaction style was identified as the most important factor, elements of which included oral communication, body language, and physical examination performance.
Regarding experiences outside the SOCC, participants reported that some providers performed only a cursory skin examination and appeared to avoid physical contact, which some patients interpreted as a sign of disrespect and a lack of racial sensitivity. Participants also expressed frustration with dermatologists outside the clinic who seemed to lack knowledge about black skin and hair disorders. Of all respondents, 71% reported they would prefer a black (or race concordant) dermatologist, including 91% of the race-concordant group and 33% of the race-discordant group.
The investigators wrote the findings underscore a number of needed changes to enhance the care of black dermatology patients, including enhanced dermatology residency and workforce education about treatment of skin of color and more training on culturally aware communication skills. Perceptions of racial and cost-of-care insensitivities identified by the study population also suggest the need for training in cultural competency and implicit bias, delivery of cost conscious care, and the social determinants of health.
As far as they know, the authors noted that, before this study, “little was known regarding black patients’ perceptions of their dermatology care, either within or external to an SOCC,” and that the study “appears to be the first to investigate and provide preliminary findings for addressing this knowledge gap.”
SOURCE: Gorbatenko-Roth K et al. JAMA Dermatol. 2019 Aug 21. doi: 10.1001/jamadermatol.2019.2063.
The study by Gorbatenko-Roth et al. will hopefully serve as a spring board for the field of dermatology to improve physicians’ cultural competence and eliminate persistent knowledge gaps that exist in the treatment of black skin and hair, according to Susan C. Taylor, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia.
In an accompanying editorial in JAMA Dermatology (2019 Aug 21. doi: 10.1001/jamadermatol.2019.1963), Dr. Taylor wrote that the analysis yields insight into the importance of recognizing and understanding that differences exist in the skin and hair of black patients, compared with those of white patients.
“Implicit in this statement is that black skin color, biology, disease, reactions, presentation, diagnosis, and treatment as well as hair types, texture, tensile strength, shape, diameter, growth pattern, follicular configuration, diseases, and treatments are different than those of whites and require the dermatologist to have an expanded knowledge base and cultural sensitivity when evaluating and treating black patients,” Dr. Taylor wrote.
Another important finding is the overall preference by black patients for a race-concordant dermatologist, Dr. Taylor wrote, noting that the ability to fulfill these preferences is limited. In 2016, black dermatologists constituted only 3% of all dermatologists in the United States, while the overall black population in the United States at the time was 12.8%.
“Although this was a small study, the authors have demonstrated the great need for improvement and opportunities for the field of dermatology, including enhanced residency training, lifelong education in skin of color, culturally sensitive and competent care, and greater diversity in the dermatology workforce,” Dr. Taylor wrote. “Let us use this article as a call to action to serve all patients, regardless of race or ethnicity, with equal excellence.”
Dr. Taylor is an associate professor of dermatology at the University of Pennsylvania, Philadelphia, and creator and inaugural director of the Skin of Color Center, St. Luke’s Roosevelt Hospital Center, New York (currently Mount Sinai St Luke’s Medical Center). She reported no disclosures other than her association with the Skin of Color Center.
The study by Gorbatenko-Roth et al. will hopefully serve as a spring board for the field of dermatology to improve physicians’ cultural competence and eliminate persistent knowledge gaps that exist in the treatment of black skin and hair, according to Susan C. Taylor, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia.
In an accompanying editorial in JAMA Dermatology (2019 Aug 21. doi: 10.1001/jamadermatol.2019.1963), Dr. Taylor wrote that the analysis yields insight into the importance of recognizing and understanding that differences exist in the skin and hair of black patients, compared with those of white patients.
“Implicit in this statement is that black skin color, biology, disease, reactions, presentation, diagnosis, and treatment as well as hair types, texture, tensile strength, shape, diameter, growth pattern, follicular configuration, diseases, and treatments are different than those of whites and require the dermatologist to have an expanded knowledge base and cultural sensitivity when evaluating and treating black patients,” Dr. Taylor wrote.
Another important finding is the overall preference by black patients for a race-concordant dermatologist, Dr. Taylor wrote, noting that the ability to fulfill these preferences is limited. In 2016, black dermatologists constituted only 3% of all dermatologists in the United States, while the overall black population in the United States at the time was 12.8%.
“Although this was a small study, the authors have demonstrated the great need for improvement and opportunities for the field of dermatology, including enhanced residency training, lifelong education in skin of color, culturally sensitive and competent care, and greater diversity in the dermatology workforce,” Dr. Taylor wrote. “Let us use this article as a call to action to serve all patients, regardless of race or ethnicity, with equal excellence.”
Dr. Taylor is an associate professor of dermatology at the University of Pennsylvania, Philadelphia, and creator and inaugural director of the Skin of Color Center, St. Luke’s Roosevelt Hospital Center, New York (currently Mount Sinai St Luke’s Medical Center). She reported no disclosures other than her association with the Skin of Color Center.
The study by Gorbatenko-Roth et al. will hopefully serve as a spring board for the field of dermatology to improve physicians’ cultural competence and eliminate persistent knowledge gaps that exist in the treatment of black skin and hair, according to Susan C. Taylor, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia.
In an accompanying editorial in JAMA Dermatology (2019 Aug 21. doi: 10.1001/jamadermatol.2019.1963), Dr. Taylor wrote that the analysis yields insight into the importance of recognizing and understanding that differences exist in the skin and hair of black patients, compared with those of white patients.
“Implicit in this statement is that black skin color, biology, disease, reactions, presentation, diagnosis, and treatment as well as hair types, texture, tensile strength, shape, diameter, growth pattern, follicular configuration, diseases, and treatments are different than those of whites and require the dermatologist to have an expanded knowledge base and cultural sensitivity when evaluating and treating black patients,” Dr. Taylor wrote.
Another important finding is the overall preference by black patients for a race-concordant dermatologist, Dr. Taylor wrote, noting that the ability to fulfill these preferences is limited. In 2016, black dermatologists constituted only 3% of all dermatologists in the United States, while the overall black population in the United States at the time was 12.8%.
“Although this was a small study, the authors have demonstrated the great need for improvement and opportunities for the field of dermatology, including enhanced residency training, lifelong education in skin of color, culturally sensitive and competent care, and greater diversity in the dermatology workforce,” Dr. Taylor wrote. “Let us use this article as a call to action to serve all patients, regardless of race or ethnicity, with equal excellence.”
Dr. Taylor is an associate professor of dermatology at the University of Pennsylvania, Philadelphia, and creator and inaugural director of the Skin of Color Center, St. Luke’s Roosevelt Hospital Center, New York (currently Mount Sinai St Luke’s Medical Center). She reported no disclosures other than her association with the Skin of Color Center.
a small study in JAMA Dermatology suggests.
Lead author Kristina Gorbatenko-Roth, PhD, of the department of psychology at University of Wisconsin-Stout, Menomonie, Wis., and colleagues analyzed the perceptions of 19 black, adult patients who had received treatment in a skin of color clinic (SOCC). Patients were asked about their perspectives and experiences inside and outside of the clinic as it pertained to dermatologists’ interaction style, cultural awareness, and overall treatment. Two focus groups consisted of patients seen by a race-concordant dermatologist, and two focus groups consisted of patients seen by a race-discordant dermatologist. The patients also responded to a survey.
Of 19 adult black patients who participated in the study, 18 respondents were women, and the mean age was 50 years. Compared with non-SOCC dermatology treatment experiences, patients experienced higher levels of overall satisfaction with SOCC dermatologists, reporting that SOCC dermatologists were better trained to care for black patients, showed greater respect and dignity, and were more trustworthy, according to the study published Aug 21.
Care satisfaction appeared most related to doctors’ interpersonal style and specialized knowledge of black skin and hair, according to the study. Investigators gleaned nine major themes during the analysis, five of which included dermatologist behaviors: interaction style, knowledge, partnering with patients in focusing on outcomes, economic sensitivity, and shared life experiences. Four themes were specific to patients: comfort, confidence, education, and concordance preference. Across all participants, a dermatologist’s interaction style was identified as the most important factor, elements of which included oral communication, body language, and physical examination performance.
Regarding experiences outside the SOCC, participants reported that some providers performed only a cursory skin examination and appeared to avoid physical contact, which some patients interpreted as a sign of disrespect and a lack of racial sensitivity. Participants also expressed frustration with dermatologists outside the clinic who seemed to lack knowledge about black skin and hair disorders. Of all respondents, 71% reported they would prefer a black (or race concordant) dermatologist, including 91% of the race-concordant group and 33% of the race-discordant group.
The investigators wrote the findings underscore a number of needed changes to enhance the care of black dermatology patients, including enhanced dermatology residency and workforce education about treatment of skin of color and more training on culturally aware communication skills. Perceptions of racial and cost-of-care insensitivities identified by the study population also suggest the need for training in cultural competency and implicit bias, delivery of cost conscious care, and the social determinants of health.
As far as they know, the authors noted that, before this study, “little was known regarding black patients’ perceptions of their dermatology care, either within or external to an SOCC,” and that the study “appears to be the first to investigate and provide preliminary findings for addressing this knowledge gap.”
SOURCE: Gorbatenko-Roth K et al. JAMA Dermatol. 2019 Aug 21. doi: 10.1001/jamadermatol.2019.2063.
a small study in JAMA Dermatology suggests.
Lead author Kristina Gorbatenko-Roth, PhD, of the department of psychology at University of Wisconsin-Stout, Menomonie, Wis., and colleagues analyzed the perceptions of 19 black, adult patients who had received treatment in a skin of color clinic (SOCC). Patients were asked about their perspectives and experiences inside and outside of the clinic as it pertained to dermatologists’ interaction style, cultural awareness, and overall treatment. Two focus groups consisted of patients seen by a race-concordant dermatologist, and two focus groups consisted of patients seen by a race-discordant dermatologist. The patients also responded to a survey.
Of 19 adult black patients who participated in the study, 18 respondents were women, and the mean age was 50 years. Compared with non-SOCC dermatology treatment experiences, patients experienced higher levels of overall satisfaction with SOCC dermatologists, reporting that SOCC dermatologists were better trained to care for black patients, showed greater respect and dignity, and were more trustworthy, according to the study published Aug 21.
Care satisfaction appeared most related to doctors’ interpersonal style and specialized knowledge of black skin and hair, according to the study. Investigators gleaned nine major themes during the analysis, five of which included dermatologist behaviors: interaction style, knowledge, partnering with patients in focusing on outcomes, economic sensitivity, and shared life experiences. Four themes were specific to patients: comfort, confidence, education, and concordance preference. Across all participants, a dermatologist’s interaction style was identified as the most important factor, elements of which included oral communication, body language, and physical examination performance.
Regarding experiences outside the SOCC, participants reported that some providers performed only a cursory skin examination and appeared to avoid physical contact, which some patients interpreted as a sign of disrespect and a lack of racial sensitivity. Participants also expressed frustration with dermatologists outside the clinic who seemed to lack knowledge about black skin and hair disorders. Of all respondents, 71% reported they would prefer a black (or race concordant) dermatologist, including 91% of the race-concordant group and 33% of the race-discordant group.
The investigators wrote the findings underscore a number of needed changes to enhance the care of black dermatology patients, including enhanced dermatology residency and workforce education about treatment of skin of color and more training on culturally aware communication skills. Perceptions of racial and cost-of-care insensitivities identified by the study population also suggest the need for training in cultural competency and implicit bias, delivery of cost conscious care, and the social determinants of health.
As far as they know, the authors noted that, before this study, “little was known regarding black patients’ perceptions of their dermatology care, either within or external to an SOCC,” and that the study “appears to be the first to investigate and provide preliminary findings for addressing this knowledge gap.”
SOURCE: Gorbatenko-Roth K et al. JAMA Dermatol. 2019 Aug 21. doi: 10.1001/jamadermatol.2019.2063.
FROM JAMA DERMATOLOGY
Key clinical point: Dermatologists need more training about the treatment of skin of color.
Major finding: Compared with a non–skin of color clinic (non-SOCC), patients experienced higher levels of overall satisfaction with SOCC dermatologists, reporting that SOCC dermatologists were better trained to care for black patients.
Study details: A study of 19 black, adult patients through focus groups and a survey.
Disclosures: No disclosures were reported.
Source: Gorbatenko-Roth K et al. JAMA Dermatol. 2019 Aug 21. doi: 10.1001/jamadermatol.2019.2063.
FRAX with BMD may not be accurate for women with diabetes
according to data from 566 women aged 40-90 years.
In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.
When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.
When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).
The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.
However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.
The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.
SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.
according to data from 566 women aged 40-90 years.
In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.
When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.
When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).
The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.
However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.
The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.
SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.
according to data from 566 women aged 40-90 years.
In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.
When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.
When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).
The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.
However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.
The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.
SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.
FROM BONE REPORTS
‘Pot’ is still hot for Dravet, Lennox-Gastaut
BANGKOK – Interim results of long-term, open-label extension trials of add-on prescription cannabidiol in patients with Dravet syndrome or Lennox-Gastaut syndrome show sustained, clinically meaningful seizure reductions with no new safety concerns, Anup D. Patel, MD, reported at the International Epilepsy Congress.
“Overall, this is a very promising and sustainable result that we were happy to see,” said Dr. Patel, chief of child neurology at Nationwide Children’s Hospital in Columbus, Ohio.
Epidiolex is the brand name for the plant-derived, highly purified cannabidiol (CBD) in an oil-based oral solution at 100 mg/mL. Dr. Patel has been involved in the medication’s development program since the earliest open-label compassionate use study, which was followed by rigorous phase 3, double-blind, placebo-controlled randomized trials, eventually leading to Food and Drug Administration marketing approval for the treatment of Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age or older.
“On June 25th, 2018, history was made: for the first time in United States history, a plant-based derivative of marijuana was approved for use as a medication, and it was also the first FDA-approved treatment for Dravet syndrome,” Dr. Patel noted at the congress sponsored by the International League Against Epilepsy.
A total of 96% of the 289 children with Dravet syndrome who completed the 14-week, double-blind, controlled randomized trials enrolled in the open-label, long-term extension study, during which they were on a median of three concurrent antiepileptic drugs along with a mean modal dose of CBD at 22 mg/kg/day. Although the target maintenance dose of CBD was 20 mg/kg/day, as advised in the product labeling, physicians could reduce or increase the dose up to 30 mg/kg/day.
“In the initial compassionate-use study, our site could go up to 50 mg/kg/day,” according to Dr. Patel. “We have plenty of data showing efficacy and continued safety beyond the FDA-recommended dose.”
In the open-label extension study, the median reduction from baseline in monthly seizure frequency assessed in 12-week intervals up to a maximum of week 72 was 44%-57% for convulsive seizures and 49%-67% for total seizures. More than 80% of patients and/or caregivers reported improvement in the patient’s overall condition as assessed on the Subject/Caregiver Global Impression of Change scale.
The pattern of adverse events associated with CBD has been consistent across all of the studies. The most common side effects are diarrhea in about one-third of patients, sleepiness in one-quarter, and decreased appetite in about one-quarter. Seven percent of patients discontinued the long-term extension trial because of adverse events.
Seventy percent of patients remained in the long-term extension study at 1 year.
Twenty-six patients developed liver transaminase levels greater than three times the upper limit of normal, and of note, 23 of the 26 were on concomitant valproic acid. None met criteria for severe drug-induced liver injury, and all recovered either spontaneously or after a reduction in the dose of CBD or valproic acid. But this association between CBD, valproic acid, and increased risk of mild liver injury has been a consistent finding across the clinical trials program.
“This is a very important clinical pearl to take away,” commented Dr. Patel, who is also a pediatric neurologist at Ohio State University.
The interim results of the long-term, open-label extension study of add-on CBD in patients with Lennox-Gastaut syndrome are similar to the Dravet syndrome study. Overall, 99% of the 368 patients with Lennox-Gastaut syndrome who completed the 14-week, double-blind, randomized trials signed up for the open-label extension. During a median follow-up of 61 weeks, the median percent reduction in seizure frequency as assessed in serial 12-week windows was 48%-70% for drop seizures and 48%-63% for total seizures. Twenty-four percent of patients withdrew from the study. Eighty-eight percent of patients or caregivers reported an improvement in overall condition when assessed at weeks 24 and 48. Forty-seven patients developed elevated transaminase levels – typically within the first 2 months on CBD – and 35 of them were on concomitant valproic acid.
More on drug-drug interactions
Elsewhere at IEC 2019, Gilmour Morrison of GW Pharmaceuticals, the Cambridge, England, company that markets Epidiolex, presented the findings of a series of drug-drug interaction studies involving coadministration of their CBD with clobazam (Sympazan and Onfi), valproate, stiripentol (Diacomit), or midazolam (Versed) in adult epilepsy patients and healthy volunteers. The researchers reported a bidirectional drug-drug interaction between Epidiolex and clobazam resulting in increased levels of the active metabolites of both drugs. The mechanism is believed to involve inhibition of cytochrome P450 2C19. However, there were no interactions with midazolam or valproate, and the slight bump in stiripentol levels when given with CBD didn’t reach the level of a clinically meaningful drug-drug interaction, according to the investigators.
On the horizon, Canadian researchers are investigating the possibility that since both the tetrahydrocannabinol (THC) and CBD components of marijuana have been shown to have anticonvulsant effects, adding a bit of THC to CBD will result in even better seizure control than with pure CBD in patients with Dravet syndrome. Investigators at Toronto’s Hospital for Sick Children have conducted a prospective, open-label study of a product containing CBD and THC in a 50:1 ratio as add-on therapy in 20 children with Dravet syndrome. The dose was 2-16 mg/kg/day of CBD and 0.04-0.32 mg/kg/day of THC. The cannabis plant extract used in the study was produced by Tilray, a Canadian pharmaceutical company.
Nineteen of the 20 patients completed the 20-week study. The sole noncompleter died of SUDEP (sudden unexpected death in epilepsy) deemed treatment unrelated. Patients experienced a median 71% reduction in motor seizures, compared with baseline. Sixty-three percent of patients had at least a 50% reduction in seizure frequency. Elevated liver transaminases occurred in patients on concomitant valproic acid, as did platelet abnormalities, which have not been seen in the Epidiolex studies, noted Dr. Patel, who was not involved in the Canadian study (Ann Clin Transl Neurol. 2018 Aug 1;5[9]:1077-88).
Dr. Patel reported serving as a consultant to Greenwich Biosciences, a U.S. offshoot of GW Pharmaceuticals. He receives research grants from that company as well as from the National Institutes of Health and the Pediatric Epilepsy Research Foundation.
BANGKOK – Interim results of long-term, open-label extension trials of add-on prescription cannabidiol in patients with Dravet syndrome or Lennox-Gastaut syndrome show sustained, clinically meaningful seizure reductions with no new safety concerns, Anup D. Patel, MD, reported at the International Epilepsy Congress.
“Overall, this is a very promising and sustainable result that we were happy to see,” said Dr. Patel, chief of child neurology at Nationwide Children’s Hospital in Columbus, Ohio.
Epidiolex is the brand name for the plant-derived, highly purified cannabidiol (CBD) in an oil-based oral solution at 100 mg/mL. Dr. Patel has been involved in the medication’s development program since the earliest open-label compassionate use study, which was followed by rigorous phase 3, double-blind, placebo-controlled randomized trials, eventually leading to Food and Drug Administration marketing approval for the treatment of Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age or older.
“On June 25th, 2018, history was made: for the first time in United States history, a plant-based derivative of marijuana was approved for use as a medication, and it was also the first FDA-approved treatment for Dravet syndrome,” Dr. Patel noted at the congress sponsored by the International League Against Epilepsy.
A total of 96% of the 289 children with Dravet syndrome who completed the 14-week, double-blind, controlled randomized trials enrolled in the open-label, long-term extension study, during which they were on a median of three concurrent antiepileptic drugs along with a mean modal dose of CBD at 22 mg/kg/day. Although the target maintenance dose of CBD was 20 mg/kg/day, as advised in the product labeling, physicians could reduce or increase the dose up to 30 mg/kg/day.
“In the initial compassionate-use study, our site could go up to 50 mg/kg/day,” according to Dr. Patel. “We have plenty of data showing efficacy and continued safety beyond the FDA-recommended dose.”
In the open-label extension study, the median reduction from baseline in monthly seizure frequency assessed in 12-week intervals up to a maximum of week 72 was 44%-57% for convulsive seizures and 49%-67% for total seizures. More than 80% of patients and/or caregivers reported improvement in the patient’s overall condition as assessed on the Subject/Caregiver Global Impression of Change scale.
The pattern of adverse events associated with CBD has been consistent across all of the studies. The most common side effects are diarrhea in about one-third of patients, sleepiness in one-quarter, and decreased appetite in about one-quarter. Seven percent of patients discontinued the long-term extension trial because of adverse events.
Seventy percent of patients remained in the long-term extension study at 1 year.
Twenty-six patients developed liver transaminase levels greater than three times the upper limit of normal, and of note, 23 of the 26 were on concomitant valproic acid. None met criteria for severe drug-induced liver injury, and all recovered either spontaneously or after a reduction in the dose of CBD or valproic acid. But this association between CBD, valproic acid, and increased risk of mild liver injury has been a consistent finding across the clinical trials program.
“This is a very important clinical pearl to take away,” commented Dr. Patel, who is also a pediatric neurologist at Ohio State University.
The interim results of the long-term, open-label extension study of add-on CBD in patients with Lennox-Gastaut syndrome are similar to the Dravet syndrome study. Overall, 99% of the 368 patients with Lennox-Gastaut syndrome who completed the 14-week, double-blind, randomized trials signed up for the open-label extension. During a median follow-up of 61 weeks, the median percent reduction in seizure frequency as assessed in serial 12-week windows was 48%-70% for drop seizures and 48%-63% for total seizures. Twenty-four percent of patients withdrew from the study. Eighty-eight percent of patients or caregivers reported an improvement in overall condition when assessed at weeks 24 and 48. Forty-seven patients developed elevated transaminase levels – typically within the first 2 months on CBD – and 35 of them were on concomitant valproic acid.
More on drug-drug interactions
Elsewhere at IEC 2019, Gilmour Morrison of GW Pharmaceuticals, the Cambridge, England, company that markets Epidiolex, presented the findings of a series of drug-drug interaction studies involving coadministration of their CBD with clobazam (Sympazan and Onfi), valproate, stiripentol (Diacomit), or midazolam (Versed) in adult epilepsy patients and healthy volunteers. The researchers reported a bidirectional drug-drug interaction between Epidiolex and clobazam resulting in increased levels of the active metabolites of both drugs. The mechanism is believed to involve inhibition of cytochrome P450 2C19. However, there were no interactions with midazolam or valproate, and the slight bump in stiripentol levels when given with CBD didn’t reach the level of a clinically meaningful drug-drug interaction, according to the investigators.
On the horizon, Canadian researchers are investigating the possibility that since both the tetrahydrocannabinol (THC) and CBD components of marijuana have been shown to have anticonvulsant effects, adding a bit of THC to CBD will result in even better seizure control than with pure CBD in patients with Dravet syndrome. Investigators at Toronto’s Hospital for Sick Children have conducted a prospective, open-label study of a product containing CBD and THC in a 50:1 ratio as add-on therapy in 20 children with Dravet syndrome. The dose was 2-16 mg/kg/day of CBD and 0.04-0.32 mg/kg/day of THC. The cannabis plant extract used in the study was produced by Tilray, a Canadian pharmaceutical company.
Nineteen of the 20 patients completed the 20-week study. The sole noncompleter died of SUDEP (sudden unexpected death in epilepsy) deemed treatment unrelated. Patients experienced a median 71% reduction in motor seizures, compared with baseline. Sixty-three percent of patients had at least a 50% reduction in seizure frequency. Elevated liver transaminases occurred in patients on concomitant valproic acid, as did platelet abnormalities, which have not been seen in the Epidiolex studies, noted Dr. Patel, who was not involved in the Canadian study (Ann Clin Transl Neurol. 2018 Aug 1;5[9]:1077-88).
Dr. Patel reported serving as a consultant to Greenwich Biosciences, a U.S. offshoot of GW Pharmaceuticals. He receives research grants from that company as well as from the National Institutes of Health and the Pediatric Epilepsy Research Foundation.
BANGKOK – Interim results of long-term, open-label extension trials of add-on prescription cannabidiol in patients with Dravet syndrome or Lennox-Gastaut syndrome show sustained, clinically meaningful seizure reductions with no new safety concerns, Anup D. Patel, MD, reported at the International Epilepsy Congress.
“Overall, this is a very promising and sustainable result that we were happy to see,” said Dr. Patel, chief of child neurology at Nationwide Children’s Hospital in Columbus, Ohio.
Epidiolex is the brand name for the plant-derived, highly purified cannabidiol (CBD) in an oil-based oral solution at 100 mg/mL. Dr. Patel has been involved in the medication’s development program since the earliest open-label compassionate use study, which was followed by rigorous phase 3, double-blind, placebo-controlled randomized trials, eventually leading to Food and Drug Administration marketing approval for the treatment of Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age or older.
“On June 25th, 2018, history was made: for the first time in United States history, a plant-based derivative of marijuana was approved for use as a medication, and it was also the first FDA-approved treatment for Dravet syndrome,” Dr. Patel noted at the congress sponsored by the International League Against Epilepsy.
A total of 96% of the 289 children with Dravet syndrome who completed the 14-week, double-blind, controlled randomized trials enrolled in the open-label, long-term extension study, during which they were on a median of three concurrent antiepileptic drugs along with a mean modal dose of CBD at 22 mg/kg/day. Although the target maintenance dose of CBD was 20 mg/kg/day, as advised in the product labeling, physicians could reduce or increase the dose up to 30 mg/kg/day.
“In the initial compassionate-use study, our site could go up to 50 mg/kg/day,” according to Dr. Patel. “We have plenty of data showing efficacy and continued safety beyond the FDA-recommended dose.”
In the open-label extension study, the median reduction from baseline in monthly seizure frequency assessed in 12-week intervals up to a maximum of week 72 was 44%-57% for convulsive seizures and 49%-67% for total seizures. More than 80% of patients and/or caregivers reported improvement in the patient’s overall condition as assessed on the Subject/Caregiver Global Impression of Change scale.
The pattern of adverse events associated with CBD has been consistent across all of the studies. The most common side effects are diarrhea in about one-third of patients, sleepiness in one-quarter, and decreased appetite in about one-quarter. Seven percent of patients discontinued the long-term extension trial because of adverse events.
Seventy percent of patients remained in the long-term extension study at 1 year.
Twenty-six patients developed liver transaminase levels greater than three times the upper limit of normal, and of note, 23 of the 26 were on concomitant valproic acid. None met criteria for severe drug-induced liver injury, and all recovered either spontaneously or after a reduction in the dose of CBD or valproic acid. But this association between CBD, valproic acid, and increased risk of mild liver injury has been a consistent finding across the clinical trials program.
“This is a very important clinical pearl to take away,” commented Dr. Patel, who is also a pediatric neurologist at Ohio State University.
The interim results of the long-term, open-label extension study of add-on CBD in patients with Lennox-Gastaut syndrome are similar to the Dravet syndrome study. Overall, 99% of the 368 patients with Lennox-Gastaut syndrome who completed the 14-week, double-blind, randomized trials signed up for the open-label extension. During a median follow-up of 61 weeks, the median percent reduction in seizure frequency as assessed in serial 12-week windows was 48%-70% for drop seizures and 48%-63% for total seizures. Twenty-four percent of patients withdrew from the study. Eighty-eight percent of patients or caregivers reported an improvement in overall condition when assessed at weeks 24 and 48. Forty-seven patients developed elevated transaminase levels – typically within the first 2 months on CBD – and 35 of them were on concomitant valproic acid.
More on drug-drug interactions
Elsewhere at IEC 2019, Gilmour Morrison of GW Pharmaceuticals, the Cambridge, England, company that markets Epidiolex, presented the findings of a series of drug-drug interaction studies involving coadministration of their CBD with clobazam (Sympazan and Onfi), valproate, stiripentol (Diacomit), or midazolam (Versed) in adult epilepsy patients and healthy volunteers. The researchers reported a bidirectional drug-drug interaction between Epidiolex and clobazam resulting in increased levels of the active metabolites of both drugs. The mechanism is believed to involve inhibition of cytochrome P450 2C19. However, there were no interactions with midazolam or valproate, and the slight bump in stiripentol levels when given with CBD didn’t reach the level of a clinically meaningful drug-drug interaction, according to the investigators.
On the horizon, Canadian researchers are investigating the possibility that since both the tetrahydrocannabinol (THC) and CBD components of marijuana have been shown to have anticonvulsant effects, adding a bit of THC to CBD will result in even better seizure control than with pure CBD in patients with Dravet syndrome. Investigators at Toronto’s Hospital for Sick Children have conducted a prospective, open-label study of a product containing CBD and THC in a 50:1 ratio as add-on therapy in 20 children with Dravet syndrome. The dose was 2-16 mg/kg/day of CBD and 0.04-0.32 mg/kg/day of THC. The cannabis plant extract used in the study was produced by Tilray, a Canadian pharmaceutical company.
Nineteen of the 20 patients completed the 20-week study. The sole noncompleter died of SUDEP (sudden unexpected death in epilepsy) deemed treatment unrelated. Patients experienced a median 71% reduction in motor seizures, compared with baseline. Sixty-three percent of patients had at least a 50% reduction in seizure frequency. Elevated liver transaminases occurred in patients on concomitant valproic acid, as did platelet abnormalities, which have not been seen in the Epidiolex studies, noted Dr. Patel, who was not involved in the Canadian study (Ann Clin Transl Neurol. 2018 Aug 1;5[9]:1077-88).
Dr. Patel reported serving as a consultant to Greenwich Biosciences, a U.S. offshoot of GW Pharmaceuticals. He receives research grants from that company as well as from the National Institutes of Health and the Pediatric Epilepsy Research Foundation.
REPORTING FROM IEC 2019
Dermatologists urged to take ownership of preventable AEs
NEW YORK – according to Galen T. Foulke, MD, who discussed avoidable clinical disasters in practice at the American Academy of Dermatology summer meeting.
Of a list of known and predictable risks that “fall under the purview of ‘You Should Have Known Better,’ ” Dr. Foulke focused on glucocorticoid-associated osteoporosis and infections associated with biologics.
Prior to delivering advice about preventing osteoporosis in patients taking glucocorticoids, he polled the audience about what they considered appropriate prophylaxis in this setting. The vast majority opted for vitamin D and calcium supplementation.
“This is a common answer, but it is the wrong answer,” said Dr. Foulke, a dermatologist affiliated with Penn State Milton S. Hershey Medical Center in Hershey, Pennsylvania.
The available data show that patients on vitamin D and calcium supplementation will continue to lose bone density on therapeutic doses of steroids, according to Dr. Foulke. This is true even when the daily doses for these supplements exceed 800 units and 900 mg, respectively. Moreover, calcium supplementation is associated with an increased risk of heart disease in patients without a calcium deficiency, he noted.
The correct answer is a bisphosphonate, said Dr. Foulke. Of the bisphosphonates, he recommended alendronate as one that is particularly well tolerated and readily reimbursed.
He believes that dermatologists prescribing glucocorticoids should not overlook the substantial risk of osteoporosis or their responsibility to discuss strategies for risk mitigation. Moreover, he believes dermatologists should consider prescribing alendronate in the appropriate candidates, not just refer to another specialist.
“In the first year of steroid use, substantial bone loss is a risk even at doses below 5 mg,” Dr. Foulke warned. At higher doses, patients can lose up to 25% of their bone density, he added.
Of preventable risks of biologics, Dr. Foulke focused on infection. In particular, he urged dermatologists who prescribe these drugs to routinely inform patients about the role and safety of vaccines in infection prevention.
“An immunosuppressant suppresses the immune system, increasing the risk of infection. It is our responsibility to protect patients from the known risks of the therapies we offer them,” he said.
Several organizations recommend the pneumococcal vaccine series and the annual influenza vaccine for patients taking biologics. Although Dr. Foulke was unable to find reliable data on vaccination rates among patients prescribed a biologic for a dermatologic indication, he cited rheumatology practice data to suggest that less than half of patients receive this protection.
A major reason for the low rate of vaccination was failure of the biologic prescriber to assume responsibility for this recommended step, according to Dr. Foulke. Although he does not believe that biologic prescribers need to administer the vaccine, and he acknowledged that he does not stock vaccines in his clinic, he does believe they should inform patients when vaccination is safe and appropriate.
Live attenuated vaccines, in his opinion, are not safe. Although he reported that this is an area of controversy, he takes a conservative approach, advising candidates for a live attenuated vaccine to undergo vaccination prior to starting the biologic or during a break from biologic therapy.
When he polled the audience about which vaccines are live attenuated vaccines, several failed to recognize that the MMR vaccine falls into this category. However, he also noted that the majority of vaccines are not live attenuated and should be considered. He specifically singled out the recombinant herpes zoster as a vaccine recommended by the American College of Rheumatology in patients on biologics.
“We do not have to give the shots, but we should be the ones who start the discussion,” said Dr. Foulke, referring to vaccines in patients on a biologic. He called these important steps “to protect patients from preventable disasters.”
Dr. Foulke reported no potential conflicts of interest.
SOURCE: Summer AAD 2019, Session F02.
NEW YORK – according to Galen T. Foulke, MD, who discussed avoidable clinical disasters in practice at the American Academy of Dermatology summer meeting.
Of a list of known and predictable risks that “fall under the purview of ‘You Should Have Known Better,’ ” Dr. Foulke focused on glucocorticoid-associated osteoporosis and infections associated with biologics.
Prior to delivering advice about preventing osteoporosis in patients taking glucocorticoids, he polled the audience about what they considered appropriate prophylaxis in this setting. The vast majority opted for vitamin D and calcium supplementation.
“This is a common answer, but it is the wrong answer,” said Dr. Foulke, a dermatologist affiliated with Penn State Milton S. Hershey Medical Center in Hershey, Pennsylvania.
The available data show that patients on vitamin D and calcium supplementation will continue to lose bone density on therapeutic doses of steroids, according to Dr. Foulke. This is true even when the daily doses for these supplements exceed 800 units and 900 mg, respectively. Moreover, calcium supplementation is associated with an increased risk of heart disease in patients without a calcium deficiency, he noted.
The correct answer is a bisphosphonate, said Dr. Foulke. Of the bisphosphonates, he recommended alendronate as one that is particularly well tolerated and readily reimbursed.
He believes that dermatologists prescribing glucocorticoids should not overlook the substantial risk of osteoporosis or their responsibility to discuss strategies for risk mitigation. Moreover, he believes dermatologists should consider prescribing alendronate in the appropriate candidates, not just refer to another specialist.
“In the first year of steroid use, substantial bone loss is a risk even at doses below 5 mg,” Dr. Foulke warned. At higher doses, patients can lose up to 25% of their bone density, he added.
Of preventable risks of biologics, Dr. Foulke focused on infection. In particular, he urged dermatologists who prescribe these drugs to routinely inform patients about the role and safety of vaccines in infection prevention.
“An immunosuppressant suppresses the immune system, increasing the risk of infection. It is our responsibility to protect patients from the known risks of the therapies we offer them,” he said.
Several organizations recommend the pneumococcal vaccine series and the annual influenza vaccine for patients taking biologics. Although Dr. Foulke was unable to find reliable data on vaccination rates among patients prescribed a biologic for a dermatologic indication, he cited rheumatology practice data to suggest that less than half of patients receive this protection.
A major reason for the low rate of vaccination was failure of the biologic prescriber to assume responsibility for this recommended step, according to Dr. Foulke. Although he does not believe that biologic prescribers need to administer the vaccine, and he acknowledged that he does not stock vaccines in his clinic, he does believe they should inform patients when vaccination is safe and appropriate.
Live attenuated vaccines, in his opinion, are not safe. Although he reported that this is an area of controversy, he takes a conservative approach, advising candidates for a live attenuated vaccine to undergo vaccination prior to starting the biologic or during a break from biologic therapy.
When he polled the audience about which vaccines are live attenuated vaccines, several failed to recognize that the MMR vaccine falls into this category. However, he also noted that the majority of vaccines are not live attenuated and should be considered. He specifically singled out the recombinant herpes zoster as a vaccine recommended by the American College of Rheumatology in patients on biologics.
“We do not have to give the shots, but we should be the ones who start the discussion,” said Dr. Foulke, referring to vaccines in patients on a biologic. He called these important steps “to protect patients from preventable disasters.”
Dr. Foulke reported no potential conflicts of interest.
SOURCE: Summer AAD 2019, Session F02.
NEW YORK – according to Galen T. Foulke, MD, who discussed avoidable clinical disasters in practice at the American Academy of Dermatology summer meeting.
Of a list of known and predictable risks that “fall under the purview of ‘You Should Have Known Better,’ ” Dr. Foulke focused on glucocorticoid-associated osteoporosis and infections associated with biologics.
Prior to delivering advice about preventing osteoporosis in patients taking glucocorticoids, he polled the audience about what they considered appropriate prophylaxis in this setting. The vast majority opted for vitamin D and calcium supplementation.
“This is a common answer, but it is the wrong answer,” said Dr. Foulke, a dermatologist affiliated with Penn State Milton S. Hershey Medical Center in Hershey, Pennsylvania.
The available data show that patients on vitamin D and calcium supplementation will continue to lose bone density on therapeutic doses of steroids, according to Dr. Foulke. This is true even when the daily doses for these supplements exceed 800 units and 900 mg, respectively. Moreover, calcium supplementation is associated with an increased risk of heart disease in patients without a calcium deficiency, he noted.
The correct answer is a bisphosphonate, said Dr. Foulke. Of the bisphosphonates, he recommended alendronate as one that is particularly well tolerated and readily reimbursed.
He believes that dermatologists prescribing glucocorticoids should not overlook the substantial risk of osteoporosis or their responsibility to discuss strategies for risk mitigation. Moreover, he believes dermatologists should consider prescribing alendronate in the appropriate candidates, not just refer to another specialist.
“In the first year of steroid use, substantial bone loss is a risk even at doses below 5 mg,” Dr. Foulke warned. At higher doses, patients can lose up to 25% of their bone density, he added.
Of preventable risks of biologics, Dr. Foulke focused on infection. In particular, he urged dermatologists who prescribe these drugs to routinely inform patients about the role and safety of vaccines in infection prevention.
“An immunosuppressant suppresses the immune system, increasing the risk of infection. It is our responsibility to protect patients from the known risks of the therapies we offer them,” he said.
Several organizations recommend the pneumococcal vaccine series and the annual influenza vaccine for patients taking biologics. Although Dr. Foulke was unable to find reliable data on vaccination rates among patients prescribed a biologic for a dermatologic indication, he cited rheumatology practice data to suggest that less than half of patients receive this protection.
A major reason for the low rate of vaccination was failure of the biologic prescriber to assume responsibility for this recommended step, according to Dr. Foulke. Although he does not believe that biologic prescribers need to administer the vaccine, and he acknowledged that he does not stock vaccines in his clinic, he does believe they should inform patients when vaccination is safe and appropriate.
Live attenuated vaccines, in his opinion, are not safe. Although he reported that this is an area of controversy, he takes a conservative approach, advising candidates for a live attenuated vaccine to undergo vaccination prior to starting the biologic or during a break from biologic therapy.
When he polled the audience about which vaccines are live attenuated vaccines, several failed to recognize that the MMR vaccine falls into this category. However, he also noted that the majority of vaccines are not live attenuated and should be considered. He specifically singled out the recombinant herpes zoster as a vaccine recommended by the American College of Rheumatology in patients on biologics.
“We do not have to give the shots, but we should be the ones who start the discussion,” said Dr. Foulke, referring to vaccines in patients on a biologic. He called these important steps “to protect patients from preventable disasters.”
Dr. Foulke reported no potential conflicts of interest.
SOURCE: Summer AAD 2019, Session F02.
EXPERT ANALYSIS FROM SUMMER AAD 2019
Class I recall issued for Sapien 3 balloon
The Food and Drug Administration has issued a class I correction recall for Edward Lifescience’s Sapien 3 balloon system, which is used to deploy transcatheter aortic valve replacements, according to a release from the agency. A class I recall is the most serious the agency issues and indicates risk of severe injury or even death.
Rather than indicate removal of the device from market, this recall provides details on how to use the device cautiously and safely and instructs physicians on proper technique to safely retract the delivery system into the sheath in cases of a suspected balloon burst. Failure to observe these recommendations can result in vascular injury, bleeding, or surgical intervention.
These recommendations and instructions reiterate those issued in an Urgent Field Safety Notice that was provided by Edward Lifesciences on July 9, 2019. Edward Lifesciences could not be reached for comment.
The Food and Drug Administration has issued a class I correction recall for Edward Lifescience’s Sapien 3 balloon system, which is used to deploy transcatheter aortic valve replacements, according to a release from the agency. A class I recall is the most serious the agency issues and indicates risk of severe injury or even death.
Rather than indicate removal of the device from market, this recall provides details on how to use the device cautiously and safely and instructs physicians on proper technique to safely retract the delivery system into the sheath in cases of a suspected balloon burst. Failure to observe these recommendations can result in vascular injury, bleeding, or surgical intervention.
These recommendations and instructions reiterate those issued in an Urgent Field Safety Notice that was provided by Edward Lifesciences on July 9, 2019. Edward Lifesciences could not be reached for comment.
The Food and Drug Administration has issued a class I correction recall for Edward Lifescience’s Sapien 3 balloon system, which is used to deploy transcatheter aortic valve replacements, according to a release from the agency. A class I recall is the most serious the agency issues and indicates risk of severe injury or even death.
Rather than indicate removal of the device from market, this recall provides details on how to use the device cautiously and safely and instructs physicians on proper technique to safely retract the delivery system into the sheath in cases of a suspected balloon burst. Failure to observe these recommendations can result in vascular injury, bleeding, or surgical intervention.
These recommendations and instructions reiterate those issued in an Urgent Field Safety Notice that was provided by Edward Lifesciences on July 9, 2019. Edward Lifesciences could not be reached for comment.